EFICACIA Y SEGURIDAD DE LA OMAVELOXOLONA EN LA ATAXIA DE FRIEDREICH

Resumen-SIIC en castellano:  Disorders 38(2):313-320. Autores: Lynch D R, Chin MP, Meyer CJ 

Filadelfia, EE.UU. En pacientes con ataxia de Friedreich, el tratamiento prolongado con omaveloxolona se asocia con beneficios sostenidos; se pone de manifiesto la importante del inicio precoz del tratamiento, ya que los pacientes que lo hacen tardíamente no llegaron a presentar la misma mejoría, respecto de los tratados tempranamente con omaveloxolona.

Conclusión Los resultados de la fase abierta de extensión del MOXIE confirman los beneficios sostenidos del tratamiento con omaveloxolona, sobre el curso natural de la enfermedad, en pacientes con AF. Se demuestra también la importancia del inicio temprano del tratamiento, ya que los beneficios observados en los pacientes del grupo omaveloxolona-omaveloxolona no fueron alcanzados por los pacientes originalmente asignados a placebo. Los pacientes que recibieron omaveloxolona desde el principio, presentaron mejora sostenida de la evolución natural de la enfermedad, al cabo de más de 2.5 años de tratamiento.

JNS-101 by Jupiter Neurosciences for Friedreich Ataxia: Likelihood of Approval

December 21, 2023. JNS-101 is under clinical development by Jupiter Neurosciences and currently in Phase II for Friedreich Ataxia. According to GlobalData, Phase II drugs for Friedreich Ataxia does not have sufficient historical data to build an indication benchmark PTSR for Phase II. 

JNS-101 is under development for the treatment of Friedreich’s ataxia. The drug candidate is a micronized formulation of pharmaceutical grade trans-resveratrol. The drug candidate is administered through oral route. It acts by targeting frataxin.

MIB-626 by Metro International Biotech for Friedreich Ataxia: Likelihood of Approval

December 21, 2023. MIB-626 is under clinical development by Metro International Biotech and currently in Phase II for Friedreich Ataxia. According to GlobalData, Phase II drugs for Friedreich Ataxia does not have sufficient historical data to build an indication benchmark PTSR for Phase II. 

MIB-626 is under development for the treatment of Friedreich’s ataxia (FA), coronavirus disease 2019 (COVID-19), acute renal failure (ARF) (acute kidney injury), mild dementia and Leber’s hereditary optic neuropathy. The drug candidate is a crystallized precursor of nicotinamide adenine dinucleotide (NAD+). It is administered through oral route. 

It was also under development for the treatment of muscle endurance (musculoskeletal disorders) and mitochondrial myopathy.

Skyclarys* (omaveloxolone) received a positive opinion from the CHMP for the treatment of Friedreich’s ataxia

Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 11-14 December 2023. Skyclarys* (omaveloxolone) received a positive opinion from the CHMP for the treatment of Friedreich’s ataxia, an inherited disease causing a range of symptoms that worsen over time, including difficulty walking, inability to co-ordinate movements, muscle weakness, speech problems, damage to the heart muscle and diabetes. 

 Skyclarys 

 INN: omaveloxolone 

Marketing-authorisation applicant: Reata Ireland Limited 

Therapeutic indication: Treatment of Friedreich’s ataxia 

Skyclarys: Pending EC decision

Biogen press release: CAMBRIDGE, Mass., Dec. 15, 2023 (GLOBE NEWSWIRE) 

Lexeo Therapeutics Reports Third Quarter 2023 Financial Results and Operational Highlights

NEW YORK, Dec. 11, 2023 (GLOBE NEWSWIRE) --LEXEO Therapeutics, Inc..Received clearance of LX2006 Clinical Trial Application (CTA) in Canada for the treatment of FA cardiomyopathy; activated first clinical trial site outside of the United States. 

 LX2006 for the Treatment of FA Cardiomyopathy: Received clearance of CTA in Canada for LX2006 for the treatment of FA cardiomyopathy and activated the first clinical trial site for the SUNRISE-FA Phase 1/2 clinical trial outside of the United States. 

LX2006 for the treatment of Friedreich’s ataxia cardiomyopathy: Interim data readout in mid-2024

Frataxin analysis using triple quadrupole mass spectrometry: application to a large heterogeneous clinical cohort

Lynch, D.R., Rojsajjakul, T., Subramony, S.H. et al. Frataxin analysis using triple quadrupole mass spectrometry: application to a large heterogeneous clinical cohort. J Neurol (2023). doi:10.1007/s00415-023-12118-x 

The present data show that assay of FXN-M and FXN-E levels in blood provides an appropriate biofluid for assessing their repletion in particular clinical contexts.

Impact of specialist ataxia centres on health service resource utilisation and costs across Europe: cross-sectional survey

Morris, S., Vallortigara, J., Greenfield, J. et al. Impact of specialist ataxia centres on health service resource utilisation and costs across Europe: cross-sectional survey. Orphanet J Rare Dis 18, 382 (2023). doi:10.1186/s13023-023-02971-4 

Within each country, resource use and costs were broadly similar for specialist ataxia centre and non-specialist ataxia centre groups. There were differences between countries in terms of health care contacts and costs.

Human frataxin, the Friedreich ataxia deficient protein, interacts with mitochondrial respiratory chain

Davide D, Federica C, Marco B, Elisa B, Silvia M, Giulia T, Federica D, Ottaviani D, Elena M, Luigi L, Elisa G, Elena Z, Antonella R, Milena B, Geppo S, Donatella C, Leonardo S, Paola C. Human frataxin, the Friedreich ataxia deficient protein, interacts with mitochondrial respiratory chain. Cell Death Dis. 2023 Dec 8;14(12):805. doi: 10.1038/s41419-023-06320-y. PMID: 38062036. 

Using healthy cells and different FRDA cellular models we found that frataxin interacts with these three respiratory complexes. Furthermore, by EPR spectroscopy, we observed that in mitochondria from FRDA patients' cells the decreased level of frataxin specifically affects the FeS cluster content of complex I. Remarkably, we also found that the frataxin-like protein Nqo15 from T. thermophilus complex I ameliorates the mitochondrial respiratory phenotype when expressed in FRDA patient's cells.

Clinical stage and plasma neurofilament concentration in adults with Friedreich ataxia

Magnus Johnsson, Henrik Zetterberg, Kaj Blennow, Christopher Lindberg, Clinical stage and plasma neurofilament concentration in adults with Friedreich ataxia, Heliyon, 2023, e23347, ISSN 2405-8440, doi:10.1016/j.heliyon.2023.e23347. 

(Last) Magnus Johnsson, Henrik Zetterberg, Kaj Blennow, Christopher Lindberg, Clinical stage and plasma neurofilament concentration in adults with Friedreich ataxia, Heliyon, Volume 10, Issue 1, 2024, e23347, ISSN 2405-8440, doi.:10.1016/j.heliyon.2023.e23347.

FRDA is less prevalent in our region of Sweden than could be assumed. In concordance with previous studies from other authors, we find that p-NfL may be increased in patients with FRDA, but less so in older more clinically affected patients. Thus, we conclude that on an individual basis, p-NFL is of uncertain clinical value as a suitable biomarker.

Intensive Multimodal Treatment for A Young Adult with Friedreich Ataxia: A Case Report

Grace Battal, Nicolas Pinsault, Berthe Hanna-Boutros. Intensive Multimodal Treatment for A Young Adult with Friedreich Ataxia: A Case Report. International Journal of Physiotherapy and Research, 2023, 11 (3), pp.4508-4516. 10.16965/ijpr.2023.110 . hal-04134585 

 The FRDA patient displayed improvement in all outcome measures. Strength, ataxia severity and functional abilities were enhanced while a higher level of independence was gained. Our observations suggest that an intensive multimodal approach holds potential in the management of FRDA and call for further research.